PMID- 29476105
OWN - NLM
STAT- MEDLINE
DCOM- 20190911
LR  - 20211204
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 8
IP  - 1
DP  - 2018 Feb 23
TI  - mTOR-dependent alterations of Kv1.1 subunit expression in the neuronal 
      subset-specific Pten knockout mouse model of cortical dysplasia with epilepsy.
PG  - 3568
LID - 10.1038/s41598-018-21656-8 [doi]
LID - 3568
AB  - Cortical dysplasia (CD) is a common cause for intractable epilepsy. 
      Hyperactivation of the mechanistic target of rapamycin (mTOR) pathway has been 
      implicated in CD; however, the mechanisms by which mTOR hyperactivation 
      contribute to the epilepsy phenotype remain elusive. Here, we investigated 
      whether constitutive mTOR hyperactivation in the hippocampus is associated with 
      altered voltage-gated ion channel expression in the neuronal subset-specific Pten 
      knockout (NS-Pten KO) mouse model of CD with epilepsy. We found that the protein 
      levels of Kv1.1, but not Kv1.2, Kv1.4, or Kvbeta2, potassium channel subunits were 
      increased, along with altered Kv1.1 distribution, within the hippocampus of 
      NS-Pten KO mice. The aberrant Kv1.1 protein levels were present in young adult 
      (>/=postnatal week 6) but not juvenile (</=postnatal week 4) NS-Pten KO mice. No 
      changes in hippocampal Kv1.1 mRNA levels were found between NS-Pten KO and WT 
      mice. Interestingly, mTOR inhibition with rapamycin treatment at early and late 
      stages of the pathology normalized Kv1.1 protein levels in NS-Pten KO mice to WT 
      levels. Together, these studies demonstrate altered Kv1.1 protein expression in 
      association with mTOR hyperactivation in NS-Pten KO mice and suggest a role for 
      mTOR signaling in the modulation of voltage-gated ion channel expression in this 
      model.
FAU - Nguyen, Lena H
AU  - Nguyen LH
AD  - Department of Neuroscience, Baylor College of Medicine, Houston, TX, USA.
AD  - The Jan and Dan Duncan Neurological Research Institute, Texas Children's 
      Hospital, Houston, TX, USA.
AD  - The Gordon and Mary Cain Pediatric Neurology Research Foundation Laboratories, 
      Texas Children's Hospital, Houston, TX, USA.
FAU - Anderson, Anne E
AU  - Anderson AE
AD  - Department of Neuroscience, Baylor College of Medicine, Houston, TX, USA. 
      annea@bcm.edu.
AD  - The Jan and Dan Duncan Neurological Research Institute, Texas Children's 
      Hospital, Houston, TX, USA. annea@bcm.edu.
AD  - The Gordon and Mary Cain Pediatric Neurology Research Foundation Laboratories, 
      Texas Children's Hospital, Houston, TX, USA. annea@bcm.edu.
AD  - Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA. 
      annea@bcm.edu.
AD  - Department of Neurology, Baylor College of Medicine, Houston, TX, USA. 
      annea@bcm.edu.
LA  - eng
GR  - R01 NS081053/NS/NINDS NIH HHS/United States
GR  - U54 HD083092/HD/NICHD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20180223
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Kv1.2 Potassium Channel)
RN  - 0 (Kv1.4 Potassium Channel)
RN  - 147173-20-4 (Kv1.1 Potassium Channel)
RN  - EC 2.7.1.1 (mTOR protein, mouse)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 3.1.3.67 (PTEN Phosphohydrolase)
RN  - EC 3.1.3.67 (Pten protein, mouse)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Animals
MH  - Disease Models, Animal
MH  - Epilepsy/complications/*genetics/pathology
MH  - Gene Expression Regulation/drug effects
MH  - Hippocampus/metabolism/pathology
MH  - Humans
MH  - Kv1.1 Potassium Channel/*genetics
MH  - Kv1.2 Potassium Channel/genetics
MH  - Kv1.4 Potassium Channel/genetics
MH  - Malformations of Cortical Development/complications/*genetics/pathology
MH  - Mice
MH  - Mice, Knockout
MH  - PTEN Phosphohydrolase/*genetics
MH  - Signal Transduction/drug effects
MH  - Sirolimus/administration & dosage
MH  - TOR Serine-Threonine Kinases/antagonists & inhibitors/*genetics
PMC - PMC5824782
COIS- The authors declare no competing interests.
EDAT- 2018/02/25 06:00
MHDA- 2019/09/12 06:00
PMCR- 2018/02/23
CRDT- 2018/02/25 06:00
PHST- 2016/04/13 00:00 [received]
PHST- 2018/02/08 00:00 [accepted]
PHST- 2018/02/25 06:00 [entrez]
PHST- 2018/02/25 06:00 [pubmed]
PHST- 2019/09/12 06:00 [medline]
PHST- 2018/02/23 00:00 [pmc-release]
AID - 10.1038/s41598-018-21656-8 [pii]
AID - 21656 [pii]
AID - 10.1038/s41598-018-21656-8 [doi]
PST - epublish
SO  - Sci Rep. 2018 Feb 23;8(1):3568. doi: 10.1038/s41598-018-21656-8.